Although the common polymorphisms associated with risk of developing prostate cancer have been investigated in a number of GWAS studies, the role of genetic variation in determining disease aggressiveness has not been well studied. We had previously identified polymorphisms near the KLK3 gene on chromosome 19q13 as being associated with disease aggressiveness and as part of a large meta-analysis of more than 25,000 cases, we have now extended that work showing that this polymorphism is associated with aggressive and high-grade prostate cancer. Few genetic risk factors have been uncovered that contribute specifically to the racial disparity in prostate cancer observed in African Americans. With the advent of Ancestry Informative Marker (AIM) single nucleotide polymorphism (SNP) panels and powerful genetic strategies such as Mapping by Admixture Linkage Disequilibrium (MALD) it is possible to discover genes that underlie ethnic variation in disease risk. Using these markers in the North Carolina-Louisiana Prostate Cancer Project we have identified areas on chromosome 8q24.21 and 11p13 associated with increased risk. Finally, we show that several common polymorphisms in one-carbon metabolism genes were associated with either DNA methylation at repetitive elements, or directly with breast cancer risk. DNA methylation can change in response to environmental exposures, such as chemical pollutants, diet, and other lifestyle factors. This study links changes in blood DNA methylation to future risk of developing cancer and may suggest lifestyle strategies for lowering risk.